Solutes that bind to plasma proteins are poorly cleared by conventional hemodialysis. Accumulation of such solutes may contribute to residual uremic illness in dialysis patients. The proposed studies will measure protein-bound solute clearances and test means for reducing protein-bound solute levels in dialysis patients. The first aim is to reduce protein-bound solute levels in patients on conventional hemodialysis. The proposed studies will test whether levels of protein-bound solutes can be reduced without any increase in dialysis time by raising the dialyzer mass transfer area coefficient and dialysate flow. The second aim is to determine how different dialysis prescriptions effect protein-bound solute levels in patients on daily nocturnal hemodialysis (DNHD). The proposed studies will test the prediction that the clearance of protein-bound solutes during DNHD can be varied independent of urea clearance, and that it can be increased by increasing dialysate flow. The third aim is to measure protein-bound solute levels in subjects enrolled in the Frequent Hemodialysis Network (FHN) trial. The proposed ancillary study to the FHN will provide a unique opportunity to relate protein-bound solute levels to other chemical parameters and indices of well-being in a large group of hemodialysis patients.